Seeing Beyond the Surface: Superior performance of Ultrasound elastography over Milan ultrasound criteria in distinguishing fibrosis of ulcerative colitis.

BACKGROUND: Colonic fibrosis has important clinical implications in ulcerative colitis. Ultrasound imaging has emerged as a convenient and reliable tool in diagnosis of inflammatory bowel disease. We aimed to explore the potential use of ultrasound to evaluate UC fibrosis. METHODS: Consecutive UC patients who had proctocolectomy from July 2022 to Sep 2023 were enrolled in the study. Patients underwent bowel ultrasound examination and ultrasound elastography imaging prior to surgery. Milan ultrasound criteria (MUC) was calculated and bowel wall stiffness was determined using two mean strain ratios (MSRs). Degree of colonic fibrosis and inflammation was measured upon histological analysis. ROC analysis was used to evaluate the performance of ultrasound-derived parameters to predict fibrosis. RESULTS: Fifty-six patients were enrolled with 112 segments included in analysis. The median fibrosis score was 2 (0-4) and the median Geboes score was 5 (0-13) and these two scores were significantly correlated (p<0.001). The muscularis mucosa thickness was significantly higher in moderate-severe fibrosis than none-mild fibrosis (p=0.003) but bowel wall thickness was not (p=0.082). The strain ratios (p<0.001) and MUC (p=0.010) was significantly higher in involved than non-involved segments. The strain ratios were correlated with fibrosis score (p<0.001) but not MUC (p=0.387). At ROC analysis, MSR1 had an AUC of 0.828 (cutoff value 3.07, 95% CI 0.746-0.893, p<0.001) to predict moderate-severe fibrosis. CONCLUSION: Ultrasound elastography imaging could predict the degree of colonic fibrosis in UC. Application of this technique could help disease monitoring and decision-making of UC patients.

IL-4 attenuates myocardial infarction injury by promoting M2 macrophage polarization.

IL-4, an immunoregulatory cytokine, plays a role in various cellular pathways and is known to regulate M2 macrophage polarization. Numerous studies have suggested that promoting the polarization of macrophages toward the M2 phenotype is beneficial for myocardial infarction (MI) recovery. However, whether IL-4 can achieve therapeutic effects in MI by regulating M2 macrophage polarization remains unclear. In this study, the authors observed that IL-4 increased the proportion of M2 macrophages in the ischemic myocardium compared to the PBS group. Additionally, IL-4 reduced the infiltration of inflammatory cells and the expression of proinflammatory-related proteins, while enhancing the expression of genes associated with tissue repair. Furthermore, IL-4 facilitated the recovery of cardiac function and reduced fibrosis in the post-MI phase. Importantly, when macrophages were depleted, the therapeutic benefits of IL-4 mentioned above were attenuated. These findings provide evidence for the effectiveness of IL-4 in treating MI through the regulation of M2 macrophage polarization, thereby encouraging further development of this therapeutic approach.

A case report: Alport syndrome and growth hormone deficiency associated with a new COL4A4 mutation.

Background: Alport syndrome (AS) is a rare progressive hereditary kidney disease that is clinically principally associated with hematuria, proteinuria, and progressive renal dysfunction. This condition not only impairs renal function but also potentially affects auditory and ocular health, significantly impacting the patient's quality of life. Case Description: This article reports a young girl with AS, combined with dwarfism attributable to growth hormone (GH) deficiency, diagnosed at Wenzhou People's Hospital in 2019. The clinical data and diagnostic steps were retrospectively analyzed. Genetic testing showed that she carried a new mutation in the COL4A4 gene, c.2317_2318delAG (p.R773Gfs*14), classified as "pathogenic" under the criteria of the American College of Medical Genetics and Genomics (ACMG), confirming her AS diagnosis. Significantly, the patient's height was more than two standard deviations (SDs) below the average for children of her race, sex, and age. The peak GH level post-stimulation was below 5 ng/mL, coupled with a growth rate of less than 5 cm/year, leading to the diagnosis of GH deficiency. Consequently, recombinant human GH (rhGH) therapy was initiated. Conclusions: After a year of rhGH treatment, we observed a notable increase in her height, without any adverse effects like elevated intracranial pressure, hypothyroidism, or worsening kidney function.

Identification of early coagulation changes associated with survival outcomes post severe burns from multiple perspectives.

Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care.

Evaluation of the impact of overlapping upper gastrointestinal symptoms on the clinical characteristics of patients with functional constipation, along with risk factor analysis.

OBJECTIVES: Functional constipation (FC), a common functional gastrointestinal disorder, is usually overlapping with upper gastrointestinal symptoms (UGS). We aimed to explore the clinical characteristics of patients with FC overlapping UGS along with the related risk factors. METHODS: The differences in the severity of constipation symptoms, psychological state, quality of life (QoL), anorectal motility and perception function, autonomic function, and the effect of biofeedback therapy (BFT) among patients with FC in different groups were analyzed, along with the risk factors of overlapping UGS. RESULTS: Compared with patients with FC alone, those with FC overlapping UGS had higher scores in the Patient Assessment of Constipation Symptoms and Self-Rating Anxiety Scale and lower scores in the Short Form-36 health survey (P < 0.05). Patients with FC overlapping UGS also had lower rectal propulsion, more negative autonomic nervous function, and worse BFT efficacy (P < 0.05). Overlapping UGS, especially overlapping functional dyspepsia, considerably affected the severity of FC. Logistic regression model showed that age, body mass index (BMI), anxiety, exercise, and sleep quality were independent factors influencing overlapping UGS in patients with FC. CONCLUSIONS: Overlapping UGS reduces the physical and mental health and the QoL of patients with FC. It also increases the difficulty in the treatment of FC. Patient's age, BMI, anxiety, physical exercise, and sleep quality might be predictors for FC overlapping UGS.

The ratio of skeletal muscle mass to body mass index combined with inflammatory immune markers to stratify survival of pancreatic cancer after pancreatoduodenectomy.

BACKGROUND: We sought to combine skeletal muscle index and inflammatory immune markers to stratify long-term survival in patients with pancreatic cancer after pancreatoduodenectomy (PD). METHODS: A total of 581 patients with pancreatic cancer underwent PD were included, and divided into the training and validation cohort. Image analysis of computed tomography scans was used to calculate the ratio of skeletal muscle (SM) area to body mass index (BMI). Naples prognostic score (NPS) was calculated from blood-test inflammatory immune markers. Propensity score matching (PSM) analysis was performed to minimize biases of clinicopathological characteristics. To estimate the overall survival (OS), a nomogram was developed using the training cohort. The predictive accuracy of nomogram was estimated by concordance index (C-index), calibration curve, and receiver operating characteristics (ROC) curve. RESULTS: After PSM analysis, SM/BMI ratio, NPS, lymph node metastasis, TNM stage, surgical margin, tumor grade and adjuvant therapy were independent predictors of OS, which were all assembled into nomogram. The SM/BMI ratio was the best single-predictor for 3- and 5-year OS, with an AUC of 0.805 (95% CI: 0.755-0.855) and 0.812 (95% CI: 0.736-0.888), respectively. Harrell's c-index of the nomogram in the training cohort was 0.786 (95% CI: 0.770-0.802), and the area under ROC curve of 1-year, 3- and 5-year OS prediction were 0.869 (95%CI: 0.837-0.901), 0.846 (95%CI: 0.810-0.882) and 0.849 (95%CI: 0.801-0.896). CONCLUSIONS: The nomogram based on SM/BMI ratio and NPS had excellent predictive performance, which should be incorporated to conventional risk scores to stratify survival of patients with PDAC after PD.

DDID: a comprehensive resource for visualization and analysis of diet-drug interactions.

Diet-drug interactions (DDIs) are pivotal in drug discovery and pharmacovigilance. DDIs can modify the systemic bioavailability/pharmacokinetics of drugs, posing a threat to public health and patient safety. Therefore, it is crucial to establish a platform to reveal the correlation between diets and drugs. Accordingly, we have established a publicly accessible online platform, known as Diet-Drug Interactions Database (DDID, https://bddg.hznu.edu.cn/ddid/), to systematically detail the correlation and corresponding mechanisms of DDIs. The platform comprises 1338 foods/herbs, encompassing flora and fauna, alongside 1516 widely used drugs and 23 950 interaction records. All interactions are meticulously scrutinized and segmented into five categories, thereby resulting in evaluations (positive, negative, no effect, harmful and possible). Besides, cross-linkages between foods/herbs, drugs and other databases are furnished. In conclusion, DDID is a useful resource for comprehending the correlation between foods, herbs and drugs and holds a promise to enhance drug utilization and research on drug combinations.

Schizandrin A enhances the sensitivity of gastric cancer cells to 5-FU by promoting ferroptosis.

Schizandrin A (Sch A) exert anticancer and multidrug resistance-reversing effects in a variety of tumors, but its effect on 5-fluorouracil (5-Fu) in gastric cancer (GC) cells remains unclear. The aim of the present study was to examine the resistance-reversing effect of Schizandrin A and assess its mechanisms in 5-Fu-resistant GC cells.5-Fu-sensitive GC cells were treated with 5-Fu and 5-Fu-resistant GC cells AGS/5-Fu and SGC7901/5-Fu were were established. These cells were stimulated with Schizandrin A alone or co-treated with 5-Fu and their effect on tumor cell growth, proliferation, migration, invasion and ferroptosis-related metabolism were investigated both in vitro and in vivo. A number of additional experiments were conducted in an attempt to elucidate the molecular mechanism of increased ferroptosis. The results of our study suggest that Schizandrin A in combination with 5-Fu might be useful in treating GC by reverse drug resistance. It was shown that Schizandrin A coadministration suppressed metastasis and chemotherapy resistance in 5-Fu-resistant GC cells through facilitating the onset of ferroptosis, which is an iron-dependent form of cell death, which was further demonstrated in a xenograft nude mouse model. Mechanistically, Schizandrin A co-administration synergistically increased the expression of transferin receptor, thus iron accumulates within cells, leading to lipid peroxidation, which ultimately results in 5-Fu-resistant GC cells death. The results of this study have provided a novel strategy for increasing GC chemosensitivity, indicating Schizandrin A as a novel ferroptosis regulator. Mechanistically, ferroptosis is induced by Schizandrin A coadministration via increasing transferrin receptor expression.

Global burden of stroke attributable to high systolic blood pressure in 204 countries and territories, 1990-2019.

Background: High systolic blood pressure (HSBP) is severely related to stroke, although the global burden of stroke associated with HSBP needs to be understood. Materials and methods: Data derived from the Global Burden of Disease, Injuries, and Risk Factors Study were used to analyze deaths, disability-adjusted life years (DALYs), age-standardized rates of mortality (ASMR), age-standardized rates of DALY (ASDR), and estimated annual percentage change (EAPC). Results: Globally, 52.57% of deaths and 55.54% of DALYs from stroke were attributable to HSBP in 2019, with higher levels in men; the ASMRs and ASDRs in 1990-2019 experienced a decline of 34.89% and 31.71%, respectively, with the highest ASMR- and ASDR-related EAPCs in women. The middle socio-demographic index (SDI) regions showed the most numbers of deaths and DALYs in 2019 and 1990, with a decline in ASMR and ASDR; East Asia shared over 33% of global deaths and DALYs; Central Asia shared the highest ASMR and ASDR; high-income Asia Pacific experienced the highest decline in the ASMR- and ASDR-related EAPCs. Central and Southeast Asia had the highest percentages for deaths and DALYs, respectively, with more ASMR in high-middle SDI; the SDI and human development index were negatively associated with ASMR/ASDR and ASMR/ASDR-related EAPCs in 2019. Conclusion: Global deaths and DALYs of stroke attributable to HSBP but none of their age-standardized rates have been on the rise over the past three decades; its disease burden focused especially on men aged 70 years and older in East, Central, and Southeast Asia, and the middle to high SDI regions.

Immediate Ansa cervicalis-to-recurrent laryngeal nerve low-tension anastomosis: A new technique for phonation recovery and bilateral anastomoses to avoid tracheotomy.

OBJECTIVE: This case series study investigated the outcomes of an innovative approach, ansa cervicalis nerve (ACN)-to-recurrent laryngeal nerve (RLN) low-tension anastomosis. METHODS: Patients who received laryngeal nerve anastomosis between May 2015 and September 2021 at the facility were enrolled. The inclusion criteria were patients with RLN dissection and anastomosis immediately during thyroid surgery. Exclusion criteria were cases with anastomosis other than cervical loop-RLN anastomosis or pronunciation recovery time > 6 months. Patients admitted before January 2020 were assigned to group A which underwent the conventional tension-free anastomosis, and patients admitted after January 2020 were group B and underwent the innovative low-tension anastomosis (Dong's method). RESULTS: A total of 13 patients were included, 11 patients received unilateral surgery, and 2 underwent bilateral surgery. For patients who underwent unilateral anastomosis, group B had a significantly higher percentage of normal pronunciation via GRBAS scale (83.3 % vs. 0 %, p = 0.015) and voice handicap index (66.7 % vs. 0 %, p = 0.002), and shorter recovery time in pronunciation (median: 1-day vs. 4 months, p = 0.001) than those in group A after surgery. CONCLUSIONS: ACNs-to-RLN low-tension anastomosis with a laryngeal segment ≤1 cm (Dong's method) significantly improves postoperative pronunciation and recovery time. The results provide clinicians with a new strategy for ACN -to-RLN anastomosis during thyroid surgery.

Impact of thyroid carcinoma invasion of recurrent laryngeal nerve on cervical lymph node metastasis.

PURPOSE: Papillary thyroid carcinoma (PTC) has a favorable prognosis. However, involvement of the recurrent laryngeal nerve (RLN) significantly increases the risk of recurrence. RLN invasion was an important factor in determining the extent of thyroid surgery. The purpose of this study was to compare clinicopathologic features and characterize risk factors of central and lateral lymph node metastasis (LLNM) of RLN invasion in patients with PTC. METHODS: A retrospective review was conducted of 130 patients with PTCs who had exclusive tumor involvement of the RLN at our institution between January 2014 and February 2019. All patients underwent total thyroidectomy and high-dose radioactive iodine (RAI) therapy. The clinicopathologic factors and prognostic outcomes of the patients with solitary and multiple RLN involvements were compared. Kaplan-Meier method was performed to compare the outcomes of tumor recurrence. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with LLNM. RESULTS: The invasion of the RLN was similar on both sides, with 58.5% on the right, 40.0% on the left, and 1.5% on both sides. Significant differences were observed in tumor size (p < 0.001), lymph node metastasis classification (p = 0.002), RLN resection (p < 0.001), and thyroglobulin (p = 0.010) in the solitary and multiple groups. During the median follow-up of 67 months, 9 (6.9%) patients developed recurrence. There were no statistical differences in recurrence for age, tumor size, gender, multifocality, lymph node metastasis (LNM), and RLN resection. According to receiver operating characteristic (ROC) curve analyses, a cut-off of tumor size > 1.7 cm was identified as the most sensitive and specific predictor of RLN with multiple involvements or LNM invasion. Univariate and multivariate analyses revealed that central lymph node metastasis (CLNM) and RLN invasion by LNM can serve as independent risk factors for LLNM (p = 0.006 and p < 0.001, respectively). CONCLUSION: Our results indicate that recurrence was comparable in patients with solitary and multiple RLN involvements. Multiple RLN involvement was associated with pathological features such as larger tumors, RLN resection, and LLNM. The presence of LNM invading RLN and multiple nerve involvement increases the risk of intraoperative RLN resection. A higher risk of multiple invasion or LNM invasion should be considered when tumor size > 1.7 cm. The presence of CLNM and RLN invaded by LNM were independent predictors for LLNM, which could aid surgeons in deciding on lateral lymph node dissection.

Enhancement of nitrogen on core taxa recruitment by Penicillium oxalicum stimulated microbially-driven soil formation in bauxite residue.

Microbially-driven soil formation process is an emerging technology for the ecological rehabilitation of alkaline tailings. However, the dominant microorganisms and their specific roles in soil formation processes remain unknown. Herein, a 1-year field-scale experiment was applied to demonstrate the effect of nitrogen input on the structure and function of the microbiome in alkaline bauxite residue. Results showed that the contents of nutrient components were increased with Penicillium oxalicum (P. oxalicum) incorporation, as indicated by the increasing of carbon and nitrogen mineralization and enzyme metabolic efficiency. Specifically, the increasing enzyme metabolic efficiency was associated with nitrogen input, which shaped the microbial nutrient acquisition strategy. Subsequently, we evidenced that P. oxalicum played a significant role in shaping the assemblages of core bacterial taxa and influencing ecological functioning through intra- and cross-kingdom network analysis. Furthermore, a recruitment experiment indicated that nitrogen enhanced the enrichment of core microbiota (Nitrosomonas, Bacillus, Pseudomonas, and Saccharomyces) and may provide benefits to fungal community bio-diversity and microbial network stability. Collectively, these results demonstrated nitrogen-based coexistence patterns among P. oxalicum and microbiome and revealed P. oxalicum-mediated nutrient dynamics and ecophysiological adaptations in alkaline microhabitats. It will aid in promoting soil formation and ecological rehabilitation of bauxite residue. ENVIRONMENT IMPLICATION: Bauxite residue is a highly alkaline solid waste generated during the Bayer process for producing alumina. Attempting to transform bauxite residue into a stable soil-like substrate using low-cost microbial resources is a highly promising engineering. However, the dominant microorganisms and their specific roles in soil formation processes remain unknown. In this study, we evidenced the nitrogen-based coexistence patterns among Penicillium oxalicum and microbiome and revealed Penicillium oxalicum-mediated nutrient dynamics and ecophysiological adaptations in alkaline microhabitats. This study can improve the understanding of core microbes' assemblies that affect the microbiome physiological traits in soil formation processes.

FERREG: ferroptosis-based regulation of disease occurrence, progression and therapeutic response.

Ferroptosis is a non-apoptotic, iron-dependent regulatory form of cell death characterized by the accumulation of intracellular reactive oxygen species. In recent years, a large and growing body of literature has investigated ferroptosis. Since ferroptosis is associated with various physiological activities and regulated by a variety of cellular metabolism and mitochondrial activity, ferroptosis has been closely related to the occurrence and development of many diseases, including cancer, aging, neurodegenerative diseases, ischemia-reperfusion injury and other pathological cell death. The regulation of ferroptosis mainly focuses on three pathways: system Xc-/GPX4 axis, lipid peroxidation and iron metabolism. The genes involved in these processes were divided into driver, suppressor and marker. Importantly, small molecules or drugs that mediate the expression of these genes are often good treatments in the clinic. Herein, a newly developed database, named 'FERREG', is documented to (i) providing the data of ferroptosis-related regulation of diseases occurrence, progression and drug response; (ii) explicitly describing the molecular mechanisms underlying each regulation; and (iii) fully referencing the collected data by cross-linking them to available databases. Collectively, FERREG contains 51 targets, 718 regulators, 445 ferroptosis-related drugs and 158 ferroptosis-related disease responses. FERREG can be accessed at https://idrblab.org/ferreg/.

Physiological and transcriptomic analyses reveal the cadmium tolerance mechanism of Miscanthus lutarioriparia.

Miscanthus lutarioriparia is a promising energy crop that is used for abandoned mine soil phytoremediation because of its high biomass yield and strong tolerance to heavy metals. However, the biological mechanism of heavy metal resistance is limited, especially for applications in the soil restoration of mining areas. Here, through the investigation of soil cadmium(Cd) in different mining areas and soil potted under Cd stress, the adsorption capacity of Miscanthus lutarioriparia was analyzed. The physiological and transcriptional effects of Cd stress on M. lutarioriparia leaves and roots under hydroponic conditions were analyzed. The results showed that M. lutarioriparia could reduce the Cd content in mining soil by 29.82%. Moreover, different Cd varieties have different Cd adsorption capacities in soils with higher Cd concentration. The highest cadmium concentrations in the aboveground and belowground parts of the plants were 185.65 mg/kg and 186.8 mg/kg, respectively. The total chlorophyll content, superoxide dismutase and catalase activities all showed a trend of increasing first and then decreasing. In total, 24,372 differentially expressed genes were obtained, including 7735 unique to leaves, 7725 unique to roots, and 8912 unique to leaves and roots, which showed differences in gene expression between leaves and roots. These genes were predominantly involved in plant hormone signal transduction, glutathione metabolism, flavonoid biosynthesis, ABC transporters, photosynthesis and the metal ion transport pathway. In addition, the number of upregulated genes was greater than the number of downregulated genes at different stress intervals, which indicated that M. lutarioriparia adapted to Cd stress mainly through positive regulation. These results lay a solid foundation for breeding excellent Cd resistant M. lutarioriparia and other plants. The results also have an important theoretical significance for further understanding the detoxification mechanism of Cd stress and the remediation of heavy metal pollution in mining soil.

SCFFBXW5-mediated degradation of AQP3 suppresses autophagic cell death through the PDPK1-AKT-MTOR axis in hepatocellular carcinoma cells.

AQP3 (aquaporin 3 (Gill blood group)), a member of the AQP family, is an aquaglyceroporin which transports water, glycerol and small solutes across the plasma membrane. Beyond its role in fluid transport, AQP3 plays a significant role in regulating various aspects of tumor cell behavior, including cell proliferation, migration, and invasion. Nevertheless, the underlying regulatory mechanism of AQP3 in tumors remains unclear. Here, for the first time, we report that AQP3 is a direct target for ubiquitination by the SCFFBXW5 complex. In addition, we revealed that downregulation of FBXW5 significantly induced AQP3 expression to prompt macroautophagic/autophagic cell death in hepatocellular carcinoma (HCC) cells. Mechanistically, AQP3 accumulation induced by FBXW5 knockdown led to the degradation of PDPK1/PDK1 in a lysosomal-dependent manner, thus inactivating the AKT-MTOR pathway and inducing autophagic death in HCC. Taken together, our findings revealed a previously undiscovered regulatory mechanism through which FBXW5 degraded AQP3 to suppress autophagic cell death via the PDPK1-AKT-MTOR axis in HCC cells.Abbreviation: BafA1: bafilomycin A1; CQ: chloroquine; CRL: CUL-Ring E3 ubiquitin ligases; FBXW5: F-box and WD repeat domain containing 5; HCC: hepatocellular carcinoma; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; 3-MA: 3-methyladenine; PDPK1/PDK1: 3-phosphoinositide dependent protein kinase 1; RBX1/ROC1: ring-box 1; SKP1: S-phase kinase associated protein 1; SCF: SKP1-CUL1-F-box protein.

C4 cereal and biofuel crop microbiomes.

Microbiomes provide multiple life-support functions for plants, including nutrient acquisition and tolerance to abiotic and biotic stresses. Considering the importance of C4 cereal and biofuel crops for food security under climate change conditions, more attention has been given recently to C4 plant microbiome assembly and functions. Here, we review the current status of C4 cereal and biofuel crop microbiome research with a focus on beneficial microbial traits for crop growth and health. We highlight the importance of environmental factors and plant genetics in C4 crop microbiome assembly and pinpoint current knowledge gaps. Finally, we discuss the potential of foxtail millet as a C4 model species and outline future perspectives of C4 plant microbiome research.

Effects of growth hormone therapy on the onset and progression of pubertal development in girls with idiopathic short stature.

OBJECTIVE: The aim of this study was to explore the impact of growth hormone (GH) therapy on the onset and progression of puberty in girls with idiopathic short stature. METHODS: This study included 541 girls aged between 4.5 and 10.6 years who were receiving GH treatment, monitored over a 22-year follow-up period. Of these, 126 girls have been followed up to the onset of menarche. The participants were divided into two groups: a ISS control group (n = 66) and a group receiving daily GH treatment at a dose of 0.15 iu/kg (n = 60). We assessed the pubertal development and GH usage of these girls every three months. RESULTS: (1) There was no significant difference in the onset of puberty between the growth hormone (GH) treatment group and the control group; however, the average duration of puberty was longer in the treatment group compared to the control group. (2) During puberty, there were no significant differences in height growth between the treated and untreated groups. (3) The duration of GH treatment showed a significant negative correlation with the age at onset of gonadal development and the age at menarche in females within the treatment group. CONCLUSION: GH treatment does not seem to accelerate the onset of puberty but may extend its duration, without significantly impacting height growth during puberty. Additionally, longer GH treatment duration is linked to earlier gonadal development and menarche in females.

Quercetin ameliorates ulcerative colitis by restoring the balance of M2/M1 and repairing the intestinal barrier via downregulating cGAS‒STING pathway.

Macrophage polarization is closely associated with the pathogenesis of ulcerative colitis (UC). Quercetin, a flavonoid, has shown promise as a treatment for inflammatory diseases, but its specific mechanism of action remains unclear. This study investigates whether quercetin can regulate intestinal macrophage polarization and promote intestinal tissue repair via the cGAS-STING pathway for the treatment of UC. In vivo, mice with 3% DSS-induced UC were intraperitoneally injected with quercetin and RU.521 for 7 days, following which their general conditions and corresponding therapeutic effects were assessed. The impact of interferon-stimulated DNA (ISD) and quercetin on macrophage polarization and the cGAS-STING pathway was investigated using RAW264.7 cells and bone marrow-derived macrophages (BMDMs) in vitro. The results demonstrated that ISD induced M1 macrophage polarization and activated the cGAS-STING pathway in vitro, while quercetin reversed ISD's inflammatory effects. In vivo, quercetin suppressed the cGAS-STING pathway in the intestinal macrophages of DSS-induced UC mice, which reduced M1 macrophage polarization, increased M2 polarization, and facilitated intestinal barrier repair in UC. Taken together, these findings provide new insights into the mechanisms via which quercetin could be used to treat UC.

Endovascular treatment of ruptured lobulated anterior communicating artery aneurysms: A retrospective study of 24 patients.

BACKGROUND: Lobulated intracranial aneurysm is a special type of aneurysm with at least one additional cyst in the neck or body of the aneurysm. Lobulated intracranial aneurysm is a complex aneurysm with complex morphology and structure and weak tumor wall, which is an independent risk factor for rupture and hemorrhage. Lobular aneurysms located in the anterior communicating artery complex account for 36.9% of all intracranial lobular aneurysms. Due to its special anatomical structure, both craniotomy and endovascular treatment are more difficult. Compared with single-capsule aneurysms, craniotomy for lobular intracranial aneurysms has a higher risk and complication rate. AIM: To investigate the efficacy and safety of endovascular treatment for ruptured lobulated anterior communicating artery aneurysm (ACoAA). METHODS: Patients with ruptured lobulated ACoAA received endovascular treatment in Sanming First Hospital Affiliated to Fujian Medical University from June 2020 to June 2022 were retrospectively included. Their demographic, clinical and imaging characteristics, endovascular treatment methods and follow-up results were collected. RESULTS: A total of 24 patients with ruptured lobulated ACoAA were included, including 9 males (37.5%) and 15 females (62.5%). Their age was 56.2 ± 8.9 years old (range 39-74). The time from rupture to endovascular treatment was 10.9 ± 12.5 h. The maximum diameter of the aneurysms was 5.1 ± 1.0 mm and neck width were 3.0 ± 0.7 mm. Nineteen patients (79.2%) were double-lobed and 5 (20.8%) were multilobed. Fisher's grade: Grade 2 in 16 cases (66.7%), grade 3 in 6 cases (25%), and grade 4 in 2 cases (8.3%). Hunt-Hess grade: Grade 0-2 in 5 cases (20.8%), grade 3-5 in 19 cases (79.2%). Glasgow Coma Scale score: 9-12 in 14 cases (58.3%), 13-15 in 10 cases (41.7%). Immediately postprocedural Raymond-Roy grade: grade 1 in 23 cases (95. 8%), grade 2 in 1 case (4.2%). Raymond-Roy grade in imaging follow-up for 2 wk to 3 months: grade 1 in 23 cases (95.8%), grade 2 in 1 case (4.2%). Follow-up for 2 to 12 months showed that 21 patients (87.5%) had good functional outcomes (modified Rankin Scale score ≤ 2), and there were no deaths. CONCLUSION: Endovascular treatment is a safe and effective treatment for ruptured lobulated AcoAA.